Tumour necrosis factor-alpha gene polymorphisms and Alzheimer's disease

Neurosci Lett. 2003 Oct 16;350(1):61-5. doi: 10.1016/s0304-3940(03)00854-1.


Recent findings suggest that production of pro-inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha), is increased in the brains of people with Alzheimer's disease (AD). We used direct sequencing methods on a section of the enhancer/promoter region and on a smaller fragment located 10.5 kb upstream of the TNF-alpha gene to respectively examine TNF-alpha polymorphisms and TNF-a and -b microsatellite alleles in a cohort of 235 post-mortem confirmed AD and 130 control cases. None of the TNF-alpha point mutations or microsatellite alleles investigated proved to be independent risk factors for AD. However, when -308/A, -238/G and TNF-a2 were examined as a 2-1-2 haplotype, we observed that the absence of that haplotype was significantly associated with AD (P = 0.014, Fisher's exact test) suggesting that the 2-1-2 haplotype may be protective against AD.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alanine / genetics
  • Alleles
  • Alzheimer Disease / genetics*
  • Case-Control Studies
  • Cohort Studies
  • Enhancer Elements, Genetic
  • Female
  • Gene Frequency
  • Glycine / genetics
  • Haplotypes
  • Humans
  • Lymphotoxin-alpha / genetics
  • Male
  • Microsatellite Repeats
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic
  • Tumor Necrosis Factor-alpha / genetics*


  • Lymphotoxin-alpha
  • Tumor Necrosis Factor-alpha
  • Alanine
  • Glycine